In the developing brain, finely specified cell interactions regulate the extensive cell migrations, patterns of cell association, and subsequent synaptic connections which establish the complex neural network. This research proposal concerns reconstruction of brain tissue from single cells in vitro for detailed investigation of these critical interactions and the spatial, temporal and informational requirements for expression of organotypic patterning. Earlier preliminary studies provided a background of histogenetic data for such investigations and culminated in the isolation of cell recognition factors from mouse cerebrum cells which markedly and specifically promoted histogenesis of homologous cerebrum cells (Garber and Moscona, 1972a,b). The present objective is further purification and characterization of these cerebrum factors and the preparation of additional specific histogenetic factors from a variety of brain cell types. Localization of the functional activity of these factors in the cell, presumably at the cell surface, will be examined by studying the interaction of dissociated cells with labeled antisera prepared against purified factors. Also, analytical studies of the enhancement process (including uptake of factors, their metabolic dependencies, competitive behavior with defined molecular moieties, and effect on neural differentiation) will be designed to clarify basic mechanisms of cell association and neural patterning in the brain. The ultimate goal is the complexing of these specific cell recognition factors to collagen or synthetic matrices to construct coded pre-neural pathways and elicit directed migration of nerve cells according to pre-determined patterns.